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It has been previously established that lung cancer could be induced in rats by exposure to radon and radon daughters. Although the oat-cell carcinomas that are common in humans were not found in rats, other histological types of lung carcinomas, especially squamous cell carcinomas and primitive lung adenocarcinomas, were similar to those observed in humans. A dose-effect relationship was established for cumulative doses varying from 25 to 3000 working-level-months (WLM), which was similar for medium and high cumulative doses to that observed in uranium miners. This experimental protocol was also used to study the potential cocarcinogenic effects of other environmental or industrial airborne pollutants such as tobacco smoke, mineral fibers, diesel exhausts, or minerals from metallic mine ores that may act synergistically with radon exposure. In rats exposed to radon and tobacco smoke combined, the incidence of lung cancers was higher by a factor of 2-4 according to the cumulative radon exposure and the duration of tobacco smoke exposure. When mineral fibers were injected intrapleurally, an increased incidence of malignant thoracic tumors was observed in rats exposed to radon and fibers combined, but synergistic effects resulted in additivity. With diesel exhausts or minerals from metallic ores, a slight, nonsignificant increase in the incidence of lung carcinomas was observed compared with rats exposed to radon alone. These results demonstrated that it is possible to establish the potential cocarcinogenic action, showing either multiplicative, additive, or no effect of various environmental or industrial airborne pollutants combined with radon exposure. This radon model is valid for investigating possible interactions between two occupational exposures. Images p64-a Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6.

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The effectiveness of fission neutrons is compared to that of gamma rays and X rays with regard to the induction of malignancies in male Sprague-Dawley rats. The analysis is based on autopsy results. It is focused on tumors that tend to be present in animals dying early, which is indicative of a high degree of lethality. The relative biological effectiveness (RBE) is deduced from a comparison of the cumulative hazard functions. Different nonparametric models-the constant relative risk model, a time shift model, and an acceleration model-are employed in the comparison, and the resulting values of RBE are seen to be substantially independent of the choice of model. The results are in good agreement with earlier studies of nonlethal lung tumors in the same series of experiments. At neutron doses of 20 to 60 mGy, the RBE of fission neutrons is about 50.

Rats were administered 237Np nitrate either intravenously or intramuscularly. Similar distributions in organs were observed after intravenous injections at pH 1.5 and 7.5. Intramuscular injections were followed by a high urinary excretion-about 30 % of the total administered dose-over the 1st month, while over 60% migrated from the injection site. The ratio of "activity eliminated via urine/activity deposited in bone" was roughly equal to 1. DTPA therapy was not effective. Neptunium behavior rather followed that of alkaline earths than that of transplutonium elements.

Three carcinogenesis modelling groups have both jointly and separately applied a multi-step carcinogenesis model with clonal expansion to one data set of lung tumours in rats exposed to radon (CEA, France). This study was designed to investigate the differences in modelling approach and fitting procedures used by the three groups in detail, and to explore possible discrepancies in the results. Using the same model assumptions and a (linear) radiation dependence on the first model step only, the three groups arrived at identical best fits, proving that the mathematical formalisms and fitting procedures do not lead to different results. However, when each group was allowed to find its own preferred fit for this data set, all three found a significantly better, but different fit to the data. All solutions indicated radiation to be an initiating agent and found additional radiation action necessary. The character of this additional radiation dependence, however, could not be unambiguously pinpointed. Tumour incidence data were described equally well when radiation dependence was taken into account in clonal expansion ("promotion") or in the second mutational step ("transformation"); extension to three model stages also resulted in an adequate description. The study showed that, although the three groups used one carcinogenesis model in principle, different model assumptions and/or different methods of finding the "best fit" could result in different descriptions of experimental data. This implies that on statistical grounds, different interpretations can be given for the action that radiation had in this data set. Different data, i.e. other data sets with age-dependent tumour data and/or information from cellular radiobiology experiments, are needed to specifically pin down the radiation dependence in the multi-step carcinogenesis process.

A colloidal suspension of radioactive cerium chloride was inoculated into the hind legs of Sprague Dawley rats. Bone and soft-tissue tumours were induced at the site of inoculation in 77% of the animals. All bone tumours were osteogenic osteosarcomas. Soft tissue tumours were mostly malignant and were of various histological types, predominantly fibrosarcomas, haemangiopericytomas, angiosarcomas and rhabdomyosarcomas. A kinetic study showed that the doubling time (DT) of tumours was closely correlated with the anatomical site of tumour development: bone tumours had a DT of 17.4 +/- 4.3 days and malignant tumours which developed in soft tissues had a DT ranging from 7.4 to 8.4 days with the exception of two haemangiosarcomas which had a long DT of 17 +/- 0.6 days. Pulmonary metastases were frequent for osteosarcomas and tumours of vascular origin. This model of induction of bone and soft-tissue tumours in rats by injection of a colloidal suspension of radioactive cerium chloride offers the possibility of more comprehensive physiopathological and kinetic studies of these tumours and may constitute a good model for their human counterparts.